Vertex Pharmaceuticals has provided a comprehensive update on recent progress in its R&D activities in cystic fibrosis (CF):
- The TRAFFIC and TRANSPORT Phase III studies of lumacaftor (VX-809) in combination with Kalydeco (ivacaftor) in people with two copies of the F508del mutation are fully enrolled. Data from these studies are expected in mid-2014, and Vertex plans to submit an NDA in the U.S. and an MAA in Europe in the second half of 2014 for the combination of lumacaftor and ivacaftor.
- Vertex has multiple studies planned and underway to evaluate whether Kalydeco may help additional people with CF who have other mutations that may respond to treatment. More than 7,000 people with CF, including those with the G551D mutation, have CFTR mutations that may respond to Kalydeco treatment. The company is also conducting studies to evaluate a combination of Kalydeco and a corrector in people with two copies of the most common CFTR mutation, F508del.
- Data from the open-label PERSIST study will be presented as a poster at NACFC. PERSIST is an ongoing rollover study of people with CF ages 6 and older with a G551D mutation who took part in the Phase III STRIVE and ENVISON studies of Kalydeco. The data from PERSIST showed that 144 weeks of continuous treatment with Kalydeco provided durable treatment effects in lung function (as measured by FEV1), weight and other measures. The safety profile was consistent with what was observed in the 48-week Phase III studies that supported the approval of Kalydeco. The PERSIST data have been submitted to the FDA for review for potential inclusion in the KALYDECO label.
- A Phase III study of people ages 6 and older with one copy of the R117H mutation is ongoing and fully enrolled. Vertex expects data to be available from this study at the end of 2013 to support a potential sNDA submission in early 2014. A potential MAA variation is planned for the second quarter of 2014.
- A Phase III study of Kalydeco in children with CF ages 2 to 5 who have a gating mutation is ongoing and fully enrolled. Data from this study are expected in the 2Q14 to support a potential sNDA submission in the second half of 2014.
- Enrollment is complete in a Phase II proof-of-concept study evaluating Kalydeco in people with CF who have clinical evidence of residual CFTR function. Data from this study are expected in the second quarter of 2014.
- Vertex recently completed enrollment of the Phase 3 TRAFFIC and TRANSPORT studies evaluating lumacaftor (VX-809) in combination with ivacaftor in people with CF ages 12 and older who have two copies (homozygous) of the F508del mutation. Vertex expects data from these studies to be available in mid-2014 to support the potential submission of an NDA and MAA for the combination in people homozygous for the F508del mutation in the second half of 2014.
- Vertex recently completed dosing in the pharmacokinetics portion of a Phase II study of VX-809 in combination with ivacaftor in children with CF ages 6 to 11 who have two copies of the F508del mutation. Enrollment in the second part of this study is expected to begin in the first quarter of 2014. Data from this study is expected be used for potential subsequent registration of the combination in children ages 6 to 11 in the U.S.
- Vertex recently began enrollment in an eight-week exploratory Phase II study of lumacaftor in combination with Kalydeco in people 18 and older with one copy (heterozygous) of the F508del mutation on one allele and a second mutation that is not expected to respond to either ivacaftor or lumacaftor alone. This study will evaluate the twice daily (q12h) administration of VX-809 (400mg) and Kalydeco (250mg) to provide additional safety and lung function data on the combination in heterozygous patients.
- Following recent discussions with regulatory authorities, Vertex is preparing to conduct a 12-week study of VX-661 in combination with Kalydeco in people with CF who have two copies of the F508del mutation. The study is designed to evaluate safety, efficacy and dose-response information to characterize VX-661 for further clinical development. Enrollment in this study is expected to begin in 1Q14, pending protocol approval from regulatory agencies.
- Vertex recently began enrollment in a Phase II study evaluating a four-week regimen of VX-661 in combination with Kalydeco in people with one copy of the G551D mutation and one copy of the F508del mutation. This is the first proof-of-concept study of a combination of a corrector and Kalydeco in people with these mutations. This study is intended to explore whether the addition of a corrector to treatment with Kalydeco can further enhance the clinical benefit received from Kalydeco alone in people with the G551D and F508del mutations. This combination treatment regimen is supported by in vitro data showing enhanced CFTR function with the combination of VX-661 and Kalydeco. Data from this study are expected in the first quarter of 2014.
- Based on the emerging profiles for VX-661 and VX-983, Vertex has prioritized VX-661 over VX-983. The company does not intend to further develop VX-983.
Vertex’s goal is to advance a next-generation corrector into clinical development by the end of 2014. Next-generation correctors could be evaluated as part of potential dual-corrector regimens. The proposed use of a dual-corrector combination regimen is supported by in vitro data that showed a combination of two correctors with Kalydeco increased chloride transport in human bronchial epithelial cells with one or two copies of the F508del mutation, as compared to the use of a single corrector in combination with Kalydeco.